N-Propargylation and Copper(I)-Catalyzed Azide-Alkyne Cycloaddition as a Convenient Strategy for Directed Post-Synthetic Modification of 4-Oxo-1,4-Dihydrocinnoline Derivatives

Abstract

4-Oxo-1,4-dihydrocinnoline derivatives as promising inhibitors of protein tyrosine phosphatase 1В were subjected to post-synthetic modification via a sequence of propargylation and copper(I)-catalyzed azide-alkyne cycloaddition reactions. The propargylation of 4-oxo- 1,4-dihydrocinnolines with propargyl bromide in the presence of various bases proceeded regioselectively at the cinnolinone N-1 atom. In the cycloaddition reaction of N-propargylcinnolinones and benzyl azide, the highest catalytic activity of copper(I) N-heterocyclic carbene complex [(IMes)Cu(Br,I)] was observed, compared to [(IMes)CuCl], [(IPr)Cu(Cl,Br,I)], and CuI.